The ever increasing demand for greater analytical productivity, i.e. in the clinical, agricultural and pharmaceutical industries, has led to the development of a variety of automated analytical instruments. The developments in this field have been stimulated by the many advantages gained through automation, e.g., increased precision, decreased cost per assay, as well as the increased reliability of automated equipment. Automated chemical analyzers can be divided into two main groups: batch analyzers and continuous flow analyzers.
In the batch analyzer, each sample is placed in its individual container within which it remains during the course of the analytical procedure. The containers proceed through the instrument on a moving belt, where reagents are added at predetermined points and times. Finally, when the treated sample reaches the detector unit (spectrophotometer, flame photometer, etc.), it is pumped into a flow through cell where the actual measuring procedure is carried out. Each sample is evaluated separately in the analyzer, i.e., it operates discontinuously. The disadvantage of batch analyzers is that they contain complex moving parts which eventually become worn during use, and there are problems associated with washing and/or discarding the containers after use. Also these instruments are less versatile than continuous flow analyzers.
In prior art continuous flow analyzers, the samples are successively aspirated from their individual containers into a tube through which the samples move until the entire analysis is completed. In this way, the samples which successively follow each other become part of a continuously moving stream into which, at predetermined points and times, reagents are continuously added at fixed flow rates. The processed stream finally reaches a flow through cell of a spectrophotometer (or other measuring device) where the signal is quantitated. The greatest advantage of continuous flow analyzers is their simplicity and their versatility which allows an easy programming of the flowing stream (which, for instance, might be split for multiple analysis). The disadvantage of the continuous flow concept is primarily the potential possibility of carry-over.
There are two types of continuous flow analyzers, the air segmented flow analyzer and the flow injection analyzer. The former separates successive samples in a continuous tube by means of air bubbles. Flow injection analysis, a relatively new method of continuous flow analysis, is based on the formation and exploitation of concentration profiles of samples injected into an unsegmented carrier stream. This procedure allows for considerably greater sampling rates than those typically found in air segmented flow analysis.
The introduction of an air bubble into a flowing stream made the continuous flow analysis practical. The role of the air bubble is simply to segment the flowing stream and thus minimize carry-over effects. Thus, in one commercially available system in which this principle is used, the continuously flowing stream is regularly and frequently segmented by air bubbles which effectively sweep the tubes, thereby allowing the sampling rate to increase up to about 100 samples per hour. A further increase of the sampling rate is hindered by the necessity of reaching, for each individual sample, a "steady state" signal level. Consequently, long sampling times are required in order to achieve the necessary precision of analysis, thus limiting the output of the continuous analyzer. Sampling rates in excess of 100 samples per hour result in carry-over effects and less precision.
Studies of the kinetic parameters which characterize continuous flow systems have established that the attainment of a "steady state" signal level is not required provided that the sample is introduced into the continuously flowing stream over an exact period of time. However, the utilization of such "transient" signals requires a high precision of sampling, which is impossible to achieve in present systems. This is due to the difficulties with precise sampling; irregularities in the pumping action of the peristaltic pump manifested by periodical pulsations of all streams; and the presence of the air bubbles.
The "flow injection analysis" system, a second type of continuous flow analyzer, introduces samples directly into a continuously flowing carrier stream. Unlike the prior art where the sampling tube continuously introduces material (sample--air--wash--air--sample, etc.) which then joins a flowing stream of reagents, the flow injection analysis is based upon discrete injection of a well defined volume of sample into a continuously flowing stream of reagents, which is then carried towards the detector. The reagents, necessary for a particular analysis, can be present in the carrier stream into which the samples are being injected. Additional reagents can be added at positions further down the line on the way to the detector.
Depending on the flow rate of the carrier system, sampling rates in excess of 300 samples per hour are attainable. This very fast sampling rate is possible because flow injection analysis utilizes "transient" signals rather than "steady state" signals which are used in air segmented flow analysis. Furthermore, the volume of reagent needed per analysis is smaller in flow injection analysis than in air segmented flow analysis. Only a small volume of sample is required (0.5 ml or less) with the flow injection analysis procedure which creates well defined, narrow segments of sample, resulting in well pronounced detector signals.
It is accordingly an object of the present invention to provide a dual channel solution handling apparatus for flow injection analysis and liquid chromatography.
It is another object of the present invention to provide a dual channel solution handling apparatus which does not require any solution or sample bypassing.
A further object of the invention is to provide a device of the type described which does not require a wash or cleaning cycle between samples.
Another object of the invention is to provide a device of the type described which does not require the use of air bubbles to separate samples.
Another object of the invention is to provide a device of the type described in which background electrolyte and samples are simultaneously injected into opposite loops permitting a high sampling rate.
A further object of the invention is to provide a device of the type described which is highly efficient in terms of maximizing sampling rate while minimizing reagent volume needed per sample as measured by the system efficiency index (SEI).
Yet another object of the invention is to provide a system which can be digitally controlled for optimizing system operation.
Other objects and advantages of the invention will be apparent from the remaining portion of the specification.